Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry.
Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry.
复制标题
评估构建非洲和欧洲血统男性前列腺癌多基因风险评分的方法。
DOI：
10.1016/j.ajhg.2023.05.010
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发表时间：
2023
影响因子：
9.8
通讯作者：
Schleutker,Johann
中科院分区：
文献类型：
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作者：
Darst,BurcuF;Shen,Jiayi;Madduri,RaviK;Rodriguez,AlexisA;Xiao,Yukai;Sheng,Xin;Saunders,EdwardJ;Dadaev,Tokhir;Brook,MarkN;Hoffmann,ThomasJ;Muir,Kenneth;Wan,Peggy;LeMarchand,Loic;Wilkens,Lynne;Wang,Ying;Schleutker,Johann
全基因组多基因风险评分(GW-PRS)已被报道具有比基于全基因组显著阈值的多基因风险评分(GW-PRS)更好的预测能力。我们比较了几种GW-PRS方法与最近开发的269个前列腺癌风险变异体的预测能力，这些变异来自多个祖先的GWAS和精细定位研究(PRS269)。GW-PRS模型是用我们以前用来建立多个家系PRS269的107,247例前列腺癌患者和127,006例对照的大而多样的前列腺癌GWA进行训练的。所产生的模型在来自加利福尼亚乌干达研究的1,586例非洲血统和1,047名对照以及来自英国生物库的8,046例欧洲血统和191,825名对照中进行了独立测试，并在来自百万退伍军人计划的13,643例欧洲血统和210,214名对照以及6,353例病例和53,362名非洲血统对照中进一步验证。在测试数据中，执行最好的GW-PRS方法的非洲和欧洲血统男性的AUC分别为0.656(95%CI=0.635-0.677)和0.844(95%CI=0.840-0.848)，对应的前列腺癌OR分别为1.83(95%CI=1.67-2.00)和2.19(95%CI=2.14-2.25)，GW-PR中每增加一个SD单位，相应的前列腺癌OR分别为1.83(95%CI=1.67-2.00)和2.19(95%CI=2.14-2.25)。与GW-PR相比，在非洲和欧洲血统男性中，PRS269具有更大或相似的AUC(分别为0.679，95%CI=0.659~0.700和AUC=0.845，95%CI=0.841~0.849)和可比的前列腺癌OR(OR=2.0595%CI=1.87~2.26和OR=2.21，95%CI=2.16~2.26)。在验证性研究中发现了类似的结果。这项研究表明，与PRS269相比，目前的GW-PRS方法可能并不能提高预测前列腺癌风险的能力。PRS269是从多个祖先的GWAS和精细定位发展而来的。
Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635–0.677) in African and 0.844 (95% CI = 0.840–0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67–2.00) and 2.19 (95% CI = 2.14–2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659–0.700 and AUC = 0.845, 95% CI = 0.841–0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87–2.26 and OR = 2.21, 95% CI = 2.16–2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269developed from multi-ancestry GWASs and fine-mapping.